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N-acetyltransferase 2, cytochrome P4502E1 and glutathione S-transferase genotypes in antitubercular treatment-induced hepatotoxicity in North Indians

Authors

  • S. V. Rana MS PhD,

    Corresponding author
    1. Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
    • Correspondence: Prof. S. V. Rana, House No 137, Sector 15 A, Chandigarh 160015, India. Tel.: +91172 2716417; fax: +91172 2744401; e-mail: svrana25@hotmail.com

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  • S. K. Sharma BS MS,

    1. Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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  • R. P. Ola BS MS,

    1. Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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  • J. K. Kamboj BS MS,

    1. Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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  • A. Malik BS MS,

    1. Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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  • R. K. Morya BS MS,

    1. Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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  • S. K. Sinha MD DM

    1. Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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Summary

What is known and objective

Tuberculosis (TB) is a major cause of illness and death in developing countries. Hepatotoxicity is a serious side effect of antituberculosis treatment (ATT). NAT2, CYP2E1 and glutathione S-transferase (GST) gene polymorphisms may play an important role in ATT-induced hepatotoxicity. So, elucidating the genetics involved in anti-TB drug-induced hepatotoxicity in patients would be of utmost clinical significance. Therefore, the objective of the study was to elucidate the role of NAT2, CYP2E1 and GST gene polymorphisms in ATT-induced hepatotoxicity in North Indian patients.

Methods

Three hundred patients with pulmonary and extra-pulmonary TB were enrolled. Total genomic DNA was isolated from each patient's peripheral lymphocytes using phenol–chloroform method, and genetic polymorphic analysis for N-acetyltransferase 2 (NAT2), cytochrome P4502E1 (CYP2E1) and GST was performed by polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP).

Results and discussion

Of the 300 patients, 185 were males and 115 females. Among them, 33 males and 22 females developed ATT-induced hepatotoxicity. There were significant increases in alanine aminotransferase, aspartate aminotransferase and bilirubin levels in patients with ATT-induced hepatotoxicity at 1 month of treatment. NAT2 5/7 and 6/7 were significantly higher in hepatotoxicity patients as compared to the non-hepatotoxicity group. c1/c1 allele of CYP2E1 gene was lower (50·9%) in ATT-induced hepatotoxicity patients as compared to non-hepatotoxicity patients (61·2%), whereas c1/c2 and c2/c2 alleles were higher, but not statistically significant. GSTM1 was significantly higher in hepatotoxicity patients as compared to non-hepatotoxicity patients, whereas GSTT1 and GSTT1/M1 were lower, but not statistically significant.

What is new and conclusion

This study indicates that patients with slow-acetylator genotypes (NAT2 5/7, 6/7) and GSTM1 allele of GST enzyme were at higher risk of ATT-induced hepatotoxicity.

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